Two hundred thirty two patients with rectal cancer at or below the peritoneal reflection, who underwent extended systematic lymphadenectomy, especially lateral node dissection, were reviewed with respect to survival rate, degree of surgical technique, and mode of recurrence. On the basis of the extent of lateral node spread, two types of lateral node dissection were performed, consisting of preservation of internal iliac vessels (conventional) and en bloc excision of these vessels (extended). The overall disease-free five-year survival rate was 69.4 percent in all patients--75.8 percent for those who underwent extended resection and 67.4 percent for those who underwent conventional resection an excellent survival rate of 49 percent of patients with lateral node metastasis was obtained. The analysis was carried out with regard to prognostic factors such as number of node metastases, obesity index, mode of recurrence, etc. We would recommend that systemic lymphadenectomy with lateral node dissection be performed for advanced rectal cancer at or below the peritoneal reflection.

Records of four hundred thirty-seven patients with lower and middle rectal cancer who underwent resection for cure at National Cancer Center Hospital from 1969 to 1983 were reviewed. There were significantly lower recurrence rates in the extended excision group compared with the conventional excision group. The recurrence rates between these two groups with Dukes' A were 0 percent (0 of 23) vs. 5.2 percent (5 of 96), those with Dukes' B were 6.3 percent (5 of 80) vs. 21.9 percent (14 of 64), Dukes' C were 23.6 percent (20 of 89) vs. 32.8 percent (28 of 85). The differences between the two groups with Dukes' B and C were statistically significant (P less than .05). The cumulative five-year survival rates in the extended excision group were 94 percent with Dukes' A stage, 88 percent with Dukes' B stage, and 61 percent with Dukes' C stage, compared with 91 percent (Dukes' A), 74 percent (Dukes' B), and 43 percent (Dukes' C) in the conventional excision group. There were also statistically significant differences between the two groups with Dukes' B and C stages (P less than .05). Although wide iliopelvic lymphadenectomy was successful as far as decreasing the incidence of local recurrence and also in prolonging survival, there were increased incidences of urine-voiding failure (loss of sense of bladder being full of urine detected in 39.4 percent of the extended excision group vs. 8.8 percent of the conventional excision group) and sexual impotency (76 percent vs. 37.5 percent).

In order to decrease the urinary and sexual morbidity which follows radical pelvic lymphadenectomy for rectal cancer, we began selective preservation of the pelvic autonomic nerves. Between 1985 and 1987, 134 patients with rectal cancer underwent a curative resection (52 abdominoperineal resections, 82 sphincter-saving resections) with extended pelvic lymphadenectomy and selective pelvic autonomic nerve preservation (PANP). PANP was classified into five degrees depending on the extent of pelvic dissection. First-degree PANP indicates complete preservation of the nerves; second-degree PANP indicates destruction of the hypogastric plexus: third-degree PANP indicates partial preservation of the pelvic autonomic plexus; fourth-degree PANP indicates bilateral or unilateral preservation of only the fourth pelvic parasympathetic nerve; and fifth-degree PANP indicates complete destruction of the pelvic autonomic nerves. Most patients with first-degree PANP were able to spontaneously void 7-10 days following the operation. However, 78 percent (28/36) of patients with fifth-degree PANP had not regained bladder sensation by the third postoperative week and were discharged with an indwelling catheter; 58 percent (21/36) had not regained bladder sensation by the 60th postoperative day. The cystometric data indicate a progressive decline in bladder sensation and function with increasingly extensive pelvic dissection. However, preservation of only the fourth parasympathetic nerve (fourth-degree PANP) resulted in partial sparing of bladder sensation and voiding function. Evaluation of sexual function in males under 60 years of age revealed that only 31 percent (12/39) recovered erectile function and only 19 percent (6/39) recovered normal ejaculatory function in the first postoperative year. Most of these patients had complete preservation of their pelvic autonomic plexus (i.e., first-degree PANP). Four patients with partial PANP have recovered erectile function. Complete PANP is the best way to prevent urinary and sexual morbidity after rectal resection. The opposing goals of maximizing the chance for cure and minimizing morbidity must be individualized and balanced in each patient. Our data demonstrate that it is now possible to perform radical pelvic lymphadenectomy in the majority of patients with advanced rectal cancer with a minimum of voiding dysfunction. Preservation of sexual function in males is more difficult and depends on complete PANP and, as such, should be restricted to the group of patients with Dukes' A and B carcinomas.

Structure-activity studies of the insulin superfamily member, relaxin-3, have shown that its G protein-coupled receptor (RXFP3) binding site is contained within its central B-chain α-helix and this helical structure is essential for receptor activation. We sought to develop a single B-chain mimetic that retained agonist activity. This was achieved by use of solid phase peptide synthesis together with on-resin ruthenium-catalyzed ring closure metathesis of a pair of judiciously placed i,i+4 α-methyl, α-alkenyl amino acids. The resulting hydrocarbon stapled peptide was shown by solution NMR spectroscopy to mimic the native helical conformation of relaxin-3 and to possess potent RXFP3 receptor binding and activation. Alternative stapling procedures were unsuccessful, highlighting the critical need to carefully consider both the peptide sequence and stapling methodology for optimal outcomes. Our result is the first successful minimization of an insulin-like peptide to a single-chain α-helical peptide agonist which will facilitate study of the function of relaxin-3.

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